International Journal of Cardiology 326 (2021) 248–251

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International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Short communication

Interpretation of elevated high-sensitivity cardiac troponin I in elite

soccer players previously infected by severe acute respiratory syndrome
coronavirus 2☆
Giuseppe Mascia a, Fabio Pescetelli b, Amedeo Baldari c, Piero Gatto d, Sara Seitun e, Paolo Sartori a,
Maurizio Pieroni f, Leonardo Calò g, Roberta Della Bona a, Italo Porto a,b,⁎
a
Cardiovascular and Thoracic Department, IRCCS Ospedale Policlinico San Martino, Genova, Italia – Italian IRCCS Cardiovascular Network
b
Università di Genova, Dipartimento di Medicina Interna e Specialità Mediche (DIMI), Genova, Italy
c
U.C. Sampdoria, Torre B, Piazza Borgo Pila, 39/Piano 5, 16129 Genova, Italy
d
Genoa Cricket and Soccer Club, Centro Sportivo PIO XII - G. Signorini, via Ronchi 67, Genova, Italy
e
Department of Radiology and Interventional Radiology, IRCCS Ospedale Policlinico San Martino, Genova, Italia – Italian IRCCS Cardiovascular Network, Italy
f
Cardiovascular Department, San Donato Hospital, Arezzo, Italy
g
Department of Cardiology, Policlinico Casillino Hospital, Rome, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: To clarify the meaning of elevated cardiac troponin in elite soccer athletes previously infected with se-
Received 24 September 2020 vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and screened for cardiovascular involvement in the
Received in revised form 6 November 2020 wake of competitive sport resumption.
Accepted 17 November 2020 Methods: We designed a retrospective cohort study with the collaboration of two Italian Serie A teams. Soccer
Available online 23 November 2020
players from both rosters (58 athletes) were systematically analysed. For every SARS-CoV-2 positive athlete,
the Italian Soccer Federation protocol requested full blood tests including high-sensitivity cardiac troponin I
Keywords:
Cardiac troponin
(hs-cTnI), along with a complete cardiovascular examination. We extended the analysis to SARS-CoV-2 negative
Elite athletes athletes.
Coronavirus disease 2019 (COVID-19) Results: A total of 13/58 players (22.4%) suffered from SARS-CoV-2infection: all had a negative cardiovascular ex-
amination and 2/13 (15%) showed increased hs-cTnI values (120.8 pg/ml and 72,6 pg/ml, respectively; upper ref-
erence level 39.2 pg/ml), which did not track with inflammatory biomarkers. Regarding the 45/58 (77.6%) non
infected athletes, a slight increase in hs-cTnI was observed in 2 (4.5%) subjects (values: 61 pg/ml and 75 pg/ml
respectively). All hs-cTnI positive athletes (4/58, 7%) underwent cardiac magnetic resonance (CMR), that ex-
cluded any cardiac injury.
Conclusions: In our retrospective study, SARS-CoV-2 infection in elite soccer athletes was not associated to clinical
or biomarkers abnormalities. Increased hs-cTnI was rare and not significantly associated with previous SARS-
COV2 infection nor with pathological findings at CMR, albeit elevated hs-cTnI was numerically more prevalent
in the infected group.
© 2020 Elsevier B.V. All rights reserved.

Coronavirus disease 2019 (COVID-19), the pandemic caused by severe
acute respiratory syndrome coronavirus 2(SARS-CoV-2), is a respiratory
illness with potential cardiovascular (CV) involvement [1,2]. Elevated
cardiac troponin (cTn), a marker of cardiac injury, is detectable in a signif-
icant proportion of COVID-19, especially in the most severe cases [3].
Myocarditis is one of the possible causes of cTn elevation and a reason
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of
the data presented and their discussed interpretation
⁎ Corresponding author at: Cardiology Unit, Ospedale Policlinico San Martino IRCCS &
Università di Genova Largo R. Benzi 15, 16132 Genoa, Italy.
E-mail address: italo.porto@unige.it (I. Porto).
for concern particularly in athletes, in which it may conspire with cardiac
adaptations to exercise, resulting in a pro-arrhythmic substrate [1].
Professional sport events have been placed on hold and distancing
has been implemented for athletes' training. In the last months, restric-
tions have been progressively lifted, and recommendations dealing with
COVID-19 in athletes have been published. In professional soccer, the
Italian federation (FIGC, Federazione Italiana Gioco Calcio) has issued
specific guidelines (http://www.sport.governo.it/it/emergenza-covid-
19/lo-sport-riparte/linee-guida-per-lo-svolgimento-degli-allenamenti-
per-gli-sport-di-squadra/).
We designed a cohort study implementing the FIGC protocol in the
wake of professional soccer resumption. Players from two Italian Serie
A teams were analysed. Both teams had a policy of extensive screening

https://doi.org/10.1016/j.ijcard.2020.11.039
0167-5273/© 2020 Elsevier B.V. All rights reserved.
G. Mascia, F. Pescetelli, A. Baldari et al. International Journal of Cardiology 326 (2021) 248–251

by reverse-transcriptase polymerase chain reaction (RT-PCR) assay for
SARS-CoV-2 in a respiratory tract swab, which was performed weekly
in the entire rosters, starting from March 1st 2020 until end June
2020. Teams' policy was to stop training for actively infected athletes,
until two negative RT-PCR; then the athletes were given another two
weeks rest before training resumption. All athletes at the time of the
study were performing a “home training” (2 h aerobic exercise super-
vised through internet by team doctors), as in-person team training
was still not allowed.
For every COVID-19 positive athlete, we measured hs-cTnI (ARCHI-
TECT STAT High Sensitive Troponin, diagnostic cut-off representing
the 99th percentile of 34.2 pg/ml in men [4]). The protocol included:
complete blood count, alanine transaminase (ALT), aspartate transami-
nase (AST), gamma-glutamyl-transferase (GGT), creatine kinase (CPK),
CPK myocardial band (CPK-MB), lactate dehydrogenase (LDH), partial
thromboplastin time (PTT), international normalized ratio (INR),
serum protein electrophoresis, ferritin, interleukin-6, C-reactive pro-
tein, D-dimer and urine test. The CV examination included clinical
visit, electrocardiogram (ECG), echocardiography, cardiopulmonary
exercise testing, and 24 h ECG Holter monitoring.
In COVID-19 negative athletes, we also measured hs-cTnI, per-
formed first level clinical examination and ECG (with second-level car-
diac tests planned only in case of abnormalities). Our study protocol also
called for cardiac magnetic resonance (CMR) in athletes with elevated
hs-cTnI, as well as for repeated measurements of biomarkers. CMR pro-
tocol included multiplane cine imaging, short-tau inversion recovery
(STIR) and late gadolinium enhancement (LGE) (see Supplementary
Methods). We collected anonymized data for the present study from
electronic and paper medical records, including demographics, cardio-
vascular risk factors and co-existing conditions.
Fifty-eight players (31 from Team-A, and 27 from Team-B) were in-
cluded, of whom 13/58 (22.4%) had suffered a previous infection. Re-
sults are reported in Table 1. Among the 13 COVID-19 positive
athletes, CV examination did not demonstrate any abnormality. Two/
13 (15%) had increased hs-cTnI (peak 120.8 pg/ml and 72.6 pg/ml),
which did not track with inflammatory biomarkers (see Table 1); hs-
cTnI was re-checked at 48 and 72 h, up to 30 days (Fig. 1) documenting
stable values. All the 45 COVID-19 negative players had a negative CV
examination. In 2/45 (4.5%) athletes we documented a slight increase
in hs-cTnI (61 pg/ml and 75 pg/ml, respectively), with stable values at
48 and 72 h, up to 30 days (Fig. 1). Chi-square statistic (see Supplemen-
tary Table) shows no relationship between COVID-19 positive status
and hs-cTnI elevation (p-value: 0.17).
CMR in the 4 hs-cTnI positive athletes, performed at 27–41 days
after COVID-19 diagnosis, ruled out any cardiac disease or injury. Cine
images revealed normal left and right ventricle volumes and systolic
function, with no segmental wall motions abnormalities; moreover,
no myocardial edema, no increased myocardial-to-skeletal muscle

Table 1
Athletes undergoing advanced cardiovascular examination. Number 1 to 13: SARS-CoV-2 positive athletes. Number 14 to 15: SARS-CoV-2 negative athletes. SARS-CoV-2 = severe acute
respiratory syndrome coronavirus 2.

Case SARS-CoV-2 ECG Echo 24 h HM Stress Hs-cTnI first Blood CMR Remarks
No. Test value exams/inflammatory
(NV: biomarkers /coagulation
39,2 pg/mL) markers*

1 Positive Negative T Normal Normal Normal, **120.8 pg/ml No abnormal values Negative Mild respiratory symptoms during
wave in DIII maximal infection
2 Positive Normal Normal Normal Normal, <39.2 pg/ml No abnormal values NP Nothing
maximal
3 Positive Normal Pericardial Normal Normal, <39.2 pg/ml No abnormal values NP Echo follow-up suggested for
effusion (3 mm) maximal minimal pericardial effusion
4 Positive Normal Normal Normal Normal, **72.6 pg/ml High-normal CK values Negative Mild respiratory symptoms during
maximal (298 U/l, ULN 304 U/l) infection
5 Positive Negative T Normal Normal Normal, <39.2 pg/ml No abnormal values NP Previously documented negative
wave in maximal T wave in
DIII, aVF DIII, aVF
6 Positive Normal Normal monomorphic Normal <39.2 pg/ml No abnormal values NP PVCs suppression during exercise
PVCs maximal test
(LVOT origin)
7 Positive Normal Normal NSVT Normal <39.2 pg/ml No abnormal values Negative Negative repeated 24 h Holter
(5 beats) maximal
8 Positive Normal Normal Normal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal
9 Positive Normal Normal Normal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal
10 Positive Normal Normal Normal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal
11 Positive Normal Normal Normal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal
12 Positive Normal Normal Normal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal
13 Positive Normal Normal Notmal Normal <39.2 pg/ml No abnormal values NP Nothing to declare
maximal

14 Negative Normal Normal Normal Normal **61 pg/ml High IL-6 (25.6 pg/ml, Negative Nothing to declare
maximal ULN 16.4 pg/ml
15 Negative Normal Normal Normal Normal **75 pg/ml Normal values Negative Documented athlete's heart
maximal

Abbreviations: No = number; NV = normal values; hs-cTnI = high sensitivity ncardiac troponin I; ECG = Electrocardiogram; Echo = Echocardiography; HM = Holter monitoring;
CMR = Cardiac magnetic resonance; FU = follow-up; NP = not performed; AV = atrioventricular; PVC = premature ventricular contraction; LVOT = left ventricular outflow tract;
NSVT = non-sustained ventricular tachycardia; ULN = upper level of normality).
* Blood exams included: complete blood count, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), creatine kinase (CPK), CPK myocardial
band (CPK-MB), lactate dehydrogenase (LDH); inflammation biomarkers included: interleukin −6 (IL-6), C-reactive protein; coagulation markers included: D-dimer, fibrinogen,
international normalized ratio (INR) ** = abnormal hs-cTnI values.

249
G. Mascia, F. Pescetelli, A. Baldari et al.
Fig. 1. Time course of high sensitive cardiac troponin in 4 athletes (2 with and 2 without previous SARS-CoV-2 infection) over 30 days. SARS-CoV-2 = severe acute respiratory syndrome
coronavirus 2.
intensity ratio on STIR images, and no pericardial effusion were
documented. Finally, LGE images were negative (see Supplementary
Figs. 1 and 2).
Raised cardiac markers in COVID-19 infection during the acute phase
are associated with poor prognosis [3]. This elevation has several poten-
tial mechanisms, including direct cardiac myocyte infection, cytokine
storm, hypoxia-mediated damage, or microvascular endothelitis [1].
The main concern for athletes with documented SARS-CoV2 infection
is the risk of active or chronic myocarditis [5]. Indeed, CMR signs consis-
tent with myocardial inflammation have been reported in up to 60% of
patients recently recovered from COVID-19 [6]. Moreover, among 26
SARS-CoV-2-positive athletes, 12/26 (46%) demonstrated LGE and 4/
26 (15%) had both abnormal T2 values and LGE by CMR [2]. It remains
unclear whether hs-cTn assay can be considered a reliable “gatekeeper”
for advanced investigations in athletes, as well as the role of CMR.
Our data may provide insights to physicians and politicians involved
in these difficult decisions, since with our systematic screening protocol,
we found no clinical or CMR evidence for myocarditis in 13 athletes
with a previous, mostly asymptomatic, SARS-CoV2 infection. Increased
hs-cTnI was rare and not significantly associated with previous SARS-
COV2 infection nor with pathological findings at CMR, albeit elevated
hs-cTnI was numerically more prevalent in the infected group. Con-
versely, we found persistently elevated hs-cTnI also in non-infected ath-
letes, raising concerns on the policy of measuring this very sensitive
myocardial injury biomarker in all SARS-CoV2 infected, irrespective of
symptoms or signs. It should be emphasized that SARS-CoV-2 does
not seem to be a cardiotropic virus. Indeed, a less than 2% prevalence
of active myocyte infection was found in 277 individuals across 22 au-
topsy studies [7]. Additionally in the acute phase, troponins, when ele-
vated, do track with inflammatory and coagulation markers,
suggesting non-specific cytokine-mediated cardiotoxicity [8]. On the
other hand, in athletes, hs-troponins can be elevated even in absence
of overt myocardial disease or injury, due to repeated exercise, espe-
cially in the young subjects [9,10].
250
International Journal of Cardiology 326 (2021) 248–251
Acknowledgement of grant support
No sources of any support for all authors in the form of grants, equip-
ment, drugs, or any combination of these.
Declaration of Competing Interest
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ijcard.2020.11.039.
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